| BACKGROUND Hepatocellular carcinoma(HCC)is a common malignant tumor with the fourth incidence rate and the second mortality rate in China.According to the annual prediction of the World Health Organization(WTO),it is estimated that more than 1 million patients will die of liver cancer in 2030,which is a difficult and intractable cancer in clinic.Due to the insidious onset of liver cancer,most patients have entered the mid to late stage at the time of initial diagnosis,and less than 30% of liver cancer patients are suitable for radical surgical treatment.However,operable patients,even after undergoing radical surgical resection and treatment,still have a high risk of recurrence and metastasis in the later stage,with poor follow-up prognosis.Gastrointestinal tumors,such as gastrointestinal tumors,already have relatively complete chemotherapy drugs and immunotargeted drugs for combined treatment,such as cisplatin(DDP),paclitaxel(PTX),5-fluorouracil(5-FU),and other chemotherapy drugs for gastric cancer combined with Pembrolizumab and Trastuzumab,However,compared to gastrointestinal tumors,the current treatment methods for primary liver cancer still urgently need to be developed and explored,especially in the field of immunotherapy,which still lacks effective new drugs,making it difficult to achieve personalized medicine(PM)for patients with liver cancer.The tumor microenvironment(TME)of hepatocellular carcinoma is related to the immune treatment response of patients with liver cancer.Analyzing the prognosis of primary and metastatic liver cancer(MHC),comparing the tumor microenvironment of primary and metastatic liver cancer,and conducting molecular typing based on the tumor microenvironment of hepatocellular carcinoma can guide the prognosis of patients with liver cancer developing immune drugs and achieving precise treatment for liver cancer patients in different immune microenvironments are of great significance.OBJECTIVE 1.This experiment will analyze the prognosis of various clinicopathological features in primary hepatocellular carcinoma and metastatic liver cancer,and determine the factors that affect their prognosis to guide the prognosis and clinical treatment.2.Compare the expression of markers in primary hepatocellular carcinoma and metastatic liver cancer,and analyze the differences to provide a theoretical basis for guiding clinical treatment.3.Based on the infiltration of immune cells in the immune microenvironment of experimental samples of primary hepatocellular carcinoma,immunomolecular typing of the immune microenvironment of primary hepatocellular carcinoma was conducted,and the impact of different markers and immune subtypes on the prognosis of hepatocellular carcinoma was explored,providing ideas for improving the prognosis of patients with hepatocellular carcinoma and developing potentially effective immune drugs.METHODS 1.Retrospective analysis: A total of 130 patients with primary hepatocellular carcinoma and metastatic liver cancer admitted to the Affiliated Hospital of Inner Mongolia Medical University from January 2017 to December 2021 with complete clinical and follow-up data were randomly selected,including 78 cases of hepatocellular carcinoma and 52 cases of metastatic liver cancer;A total of 65 patients with complete clinical and follow-up data suitable for immunohistochemistry were selected with the consent of the patient and their family members and strict pathological screening,including 49 cases of hepatocellular carcinoma and 16 cases of metastatic liver cancer.2.Immunohistochemistry(IHC)was used to detect the expression levels of CD20,CD8,CD15,and Foxp 3 in the collected pathological samples of primary and metastatic liver cancer,and to compare the differences in the expression of markers within the immune microenvironment of the two types of tumors.3.According to the expression of CD20 and CD8 in primary hepatocellular carcinoma,they were scored and divided into three immune subtypes: high(CD20 high expression,CD8 high expression),medium(CD20 medium or low expression,CD8 medium expression),and low(CD20 low expression,CD8 low expression).4.Use statistical software SPSS27.0 to process and analyze the data,analyze the prognostic factors of primary hepatocellular carcinoma and metastatic liver cancer,compare the differences in immune cells within the two tumor microenvironments,analyze the expression of tumor related neutrophils and regulatory T cells in different immune subtypes of primary liver cancer,and explore the impact of different immune cells and molecular subtypes on the prognosis of primary hepatocellular carcinoma.RESULTS 1.In this study,130 clinical data were included in the prognosis analysis,including 78 cases of primary hepatocellular carcinoma and 52 cases of metastatic liver cancer.The following results were obtained by substituting follow-up record related factors into the Kaplan Meier survival analysis.In primary hepatocellular carcinoma,Child-Pugh grade,histological grade,and recurrence and metastasis factors are significant risk factors that affect the prognosis of hepatocellular carcinoma,with statistical significance(P<0.05).Other clinicopathological characteristics such as age,gender,tumor number,tumor size,AFP,smoking,alcohol consumption,history of liver disease,Foxp3 expression,postoperative chemotherapy,postoperative radiotherapy Immunotherapy and other factors were not significant risk factors affecting the prognosis of primary hepatocellular carcinoma,with no statistical difference(P>0.05).In multivariate Cox regression analysis,factors affecting prognosis were substituted.Child-Pugh grade C,histological grade,and recurrence and metastasis were independent risk factors affecting the prognosis of patients with primary hepatocellular carcinoma(P<0.05).Among metastatic liver cancer,history of liver disease,postoperative chemotherapy,surgical treatment,and recurrence and metastasis factors are significant risk factors for the prognosis of metastatic liver cancer,with statistical significance(P<0.05).Other factors such as tumor source,tumor number,tumor size,and alcohol consumption are not prognostic factors for metastatic liver cancer,with no statistical significance(P>0.05),Factors affecting the prognosis of metastatic liver cancer were substituted into multivariate Cox regression analysis.Surgical treatment was an independent risk factor affecting the prognosis of metastatic liver cancer(P<0.05).2.Descriptive analysis and nonparametric testing of the expression values of four sets of immune markers in primary hepatocellular carcinoma and metastatic liver cancer showed that the expressions of CD20,CD8,CD15,and Foxp3 in primary hepatocellular carcinoma were higher than those in metastatic liver cancer,and there was a statistically significant difference in the expression of CD20 in the two tumor microenvironments(P<0.05).3.According to the expression of CD20 and CD8 in the tumor microenvironment of primary hepatocellular carcinoma,primary hepatocellular carcinoma was divided into high,medium,and low immune subtypes.The expression trend of CD15 and Foxp3 in different molecular typing was analyzed by box graph.The Kaplan Meier survival analysis results showed that there was a statistical difference between the expression of CD20,CD8,CD15,and a large amount of Foxp3 and the molecular typing on the prognosis of primary hepatocellular carcinoma(P<0.05).CONCLUSIONS 1.In primary hepatocellular carcinoma,Child-Pugh grade,histological grade,recurrence,and metastasis are risk factors that affect prognosis,while Child-Pugh grade C,histological grade,and recurrence,metastasis are independent risk factors that affect prognosis;In metastatic liver cancer,history of liver disease,postoperative chemotherapy,surgical treatment,and recurrence and metastasis factors are prognostic risk factors for metastatic liver cancer,while surgery is an independent risk factor affecting prognosis.It is suggested that for patients with advanced liver cancer who have poor liver function and cannot undergo radical surgical treatment,the development of new immune drugs to control the development of liver cancer,as well as recurrence and metastasis,has important value in improving the prognosis of patients.2.The infiltration of B lymphocytes,cytotoxic T cells,tumor related neutrophils,and regulatory T cells in the tumor microenvironment of primary hepatocellular carcinoma is more frequent than that of metastatic liver cancer.There are differences in the infiltration of B lymphocytes in the tumor microenvironment of the two,suggesting that B lymphocytes are an important immune driving force.3.B-lymphocytes,cytotoxic T cells,tumor related neutrophils,a large number of regulatory T cells,and molecular typing are factors that affect the prognosis of primary hepatocellular carcinoma.B-lymphocytes and cytotoxic T cells are protective factors for the prognosis of hepatocellular carcinoma,and they are positive immune cells;Tumor associated neutrophils and a large number of regulatory T cells are risk factors for the prognosis of hepatocellular carcinoma,and they are negative immunocytes.The prognosis of high immune subtypes is significantly better than that of medium and low immune subtypes.Increasing the infiltration of positive immune cells and stimulating their immune activity,reducing the infiltration of negative immune cells and inhibiting their function can help improve the prognosis of patients with primary hepatocellular carcinoma.4.High infiltration of regulatory T cells plays a catalytic role in the development of primary hepatocellular carcinoma.Developing immunotargeted drugs that inhibit the development and maturation of regulatory T cells is expected to inhibit tumor development and improve patient prognosis. |
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